Herpes Simplex Viruses. HSV-1 HSV-2 Herpesvirus hominis Infection mucocutaneous surfaces, CNS

Size: px

Start display at page:

Download "Herpes Simplex Viruses. HSV-1 HSV-2 Herpesvirus hominis Infection mucocutaneous surfaces, CNS"

Rudolf Doyle
6 years ago
Views:

1 Viral disorders

3 Herpes Simplex Viruses HSV-1 HSV-2 Herpesvirus hominis Infection mucocutaneous surfaces, CNS

4 Etiologic agent Double-stranded DNA HSV-1, -2 Latency: viral genomes present in neuronl cells in a repressed state Reactivation: release of HSV from the neuron anf entry into epithelial cells viral replication reappearence of virus on mucosal surfaces

5 Pathogenesis Virus transported intra-axonally to the nerve cell bodies in ganglia Virus spreads to mucocutaneous surfaces via peripheral sensory nerves

6 Immunity Host immune response T cell reponses

7 Epidemiology Infection with HSV-1 acqired frequently 90% of adults Abs to HSV-1 by the fifth decade 15-20% Abs to HSV-2

8 Clinical spectrum Incubation period: 1 to 26 days Oral-facial infections Genital infections

9 Oral-Facial Infections Primary HSV infection children and young adults gingivostomatitis +pharyngitis: fever, inability to eat, cervical lymphadenopathy Hard and soft palate, gingiva, tongue, lip Reactivation of HSV-1 infection recurrent herpes labialis Reactivation of HSV from the trigeminal ganglia virus excretion in the saliva, iintraoral mucosal ulceratins, herpetic ulcerations on the lip and external facial skin

11 Genital Infections Fever, pain, itching, vaginal and urethral discharge, tender inguinal lymphadenopathy, bilateral lesions of the external genitalia: vesicles, painful ulcers

13 Herpetic Whitlow HSV infection of the finger Infction mya recur

15 Eye Infections Corneal blindness HSV keratitis Chorioretinitis

16 Central and Peripheral Nervous System Infections HSV encephalitis: fever, focal neurologic symptoms HSV DNA detection by PCR in cerebrospinal fluid HSV aseptic meningitis

17 Visceral Infections HSV esophagitis HSV pneumonitis HSV hepatitis HSV monoarticular arthritis HSV glomerulonephritis

18 Diagnosis Clinical diagnosis: characteristic multiple vesicular lesions on an erythematosus base HSV DNA detection by PCR

20 Treatment Acyclovir Ganciclovir Famciclovir Valacyclovir Topical use HSV encephalitis: iv. Acyclovir Effective in shortening the duration of symptoms Acyclovir-resistant case: Foscamet, Cidofovir

21 Varicella-Zoster Virus VZV Varicella (chickenpox): extremely contagious infection, childhood, exanthematous vesicular rash Herpes zoster (shingles): dermatomal vesicular rash, severe pain

22 Etiology Herpesviridae family Double-stranded DNA

23 Primary Infection Transmission by the respiratory route Nasopharynx: virus replication Viremia Dermal vesicles Epidermal hemorrhage Vesicular fluid becomes cloudy Rupture of vesicles fluid release with infectious viruses

24 Recurrent Infection Reactivation of VZV herpes zoster Virus infects dorsal root ganglia during chickenpox remains latent reactivation

25 Chickenpox Epidemiology and Clinical manifestations Highly contagious Children 5-9 years old affected Incubation period: days Patients are infectious: 48 hours before onset of the vesicular rash, 4-5 days during the period of vesicle formation, until all vesicles crusted Skin lesions: maculopapules, vesicles, and scabs in various stages of evolution on the trunk, face Varicella pneumonia

29 Herpes Zoster Reactivation of latent VZV from dorsal ganglia Unilateral vesicular eruption within a dermatome Zoster-associated pain: severe Zoster ophthalmicus: ophthalmic branch of the trigeminal nerve involved blindness Duration of disease Postherpetic neuralgia CNS: meningoencephalitis Pneumonitis, hepatitis

33 Laboratory findings Rarely required VZV DNA by PCR in vesicular fluid

34 Treatment Meticulous skin care Acyclovir 5x800 mg orally 5-7 days Iv. Acyclovir Valacyclovir Famciclovir Analgesics : Gabapentin, Pregabalin, Lidocain

35 Prevention Live attenuated varicella vaccine = Oka vaccine in children up to 12 years of age VZIG = varicella-zoster immune globulin

36 Epstein-Barr Virus Infections Infectious Mononucleosis Fever, sore throat, lympadenopathy, atypical lymphocytosis Nasopharyngeal carcinoma, Burkitt s lymphoma, Hodgkin s disease, B cell lymphoma Herpesviridae, linear DNA

37 Epidemiology EBV: disease of young adults Kissing disease Spread: contact with oral secretions

38 Pathogenesis Virus infects oropharynx and salivary glands Proliferation and expansionof EBVinfected B cells Lympadenopathy

39 Clinical Symptoms Fever, pharyngitis, tonsillitis, cervical lymphadenopathy, splenomegaly, hepatomegaly After Ampicillin treatment macular rash

41 Laboratory Findings WBC Lymphocytosis, atypical lymphocytes SeBi, ALT, AST, SAP

42 Complications Splenic rupture CNS: meningitis, encephalitis Upper airway obstruction hypertrophy of lymphoid tissue in the tonsils or adenoids AIHA Hepatitis

43 Diagnosis. Serologic Testing Heterophile test or monospot test + Anti-VCA (viral capsid antigen) IgM + Anti-EA-D (antibody to early antigen of infected cells) +

44 Treatment Bed rest, analgesia Prednisone?

45 Cytomegalovirus Mononucleosis syndrome Double-strand DNA Atypical lymphocytes in the peripheral blood

46 Clinical Manifestations Fever, myalgia, headche, splenomegaly Relative lymphocytosis with atypical lymphocytes ALT, AST, SAP Cryoglobulin, rheumatoid factor, cold agglutinin, ANA

47 CMV Infection in the Immuncompromised Host After organ transplantation CMV pneumonia CMV retinitis blindness CMV hepatitis CMV meningoencephalitis

48 Diagnosis CMV DNA by PCR CMV-specific IgM

49 Treatment Ganciclovir Valganciclovir Foscarnet Cidofovir

50 Human Immunodeficiency Virus Disease: AIDS HIV etiologic agent Human retrovirus HIV-1 most common cause USA HIV-2 WEst Africa

51 HIV structure

52 HIV Transmission Homosexual and heterosexual contact Blood and blood products Infected mothers to infants: intrapartum, perinatally, via breast milk

53 HIV Epidemiology Global pandemic million individuals with HIV worldwide

56 Pathogenesis Progressive quantitative and qualitative deficiency of T CD4+ helper lymphocytes immunodeficiency CD4+ infections and neoplasms AIDS-defining illnesses

57 Typical course of an untreated HIV-infected individual

58 Diagnosis of HIV Infection Antibodies to HIV appear in the circulation 2-12 weeks following infection ELISA for standard blood screening, sensitivity > 99,5% Confirmation: Western blot for detection of Abs to HIV Direct detection of HIV: immune complexdissociated p24 antigen capture assay, HIV RNA by PCR

59 Laboratory monitoring CD4+ T cell count: <200/μl Level of HIV RNA in serum

60 Clinical manifestations Acute syndrome Asymptomatic state Advanced disease

61 The acute HIV syndrome 3-6 weeks after primary infection Fever, pharyngitis, lymphadenopathy, headache, arthralgias, myalgias, anorexia, weigh loss, nausea, vomiting diarrhoea Neurologic: meningitis, encephalitis, myelopahy, peripheral neuropathy

63 The asymptomatic stage Clinical latency 10 years

64 Symptomatic disease Cd4+ T cell count < 200/μl HIV-associated diseases: Pneumocystis carini/jiroveci pneumonia, Toxoplasmosis of brain,atypical mycobacteria, Wasting syndrome, Lymphoma of brain, Kaposi s sarcoma, Encephalopathy, HIVassociated dementia, Aphthous ulcer, Oral hairy leukoplakia

67 Initial evaluation of the patient with HIV History taking and physical examination Routine chemistry and hematology CD4+ T lymphocyte count Two plasma HIV RNA levels HIV resistance testing Mini-mental status examination

68 Treatment Good control of HIV replication through the use of combination ART therapy ART (antiretroviral therapy) HAART (highly active antiretroviral therapy)

71 Antiretroviral drugs used in the treatment of HIV Reverse Transcriptase Inhibitors Zidovudine (AZT, aidothymidine, Retrovir) Didanosine (Videx) Zalcitabine (HIVID) Stavudine (Zerit) Lamivudine (Epivir) Abacivir (Ziagen) Tenofir (Viread) Delavirdine (Rescriptor) Nevirapine (Viramune)

72 Antiretroviral drugs 2. Protease Inhibitors Saquinavir mesylate Ritonavir (Norvir) Indinavir sulfate (Crixivan) Nefinavir mesylate (Viracept) Darunavir (Prezista) Tipranavir (Aptivus)

73 Antiretroviral drugs 3. Entry Inhibitors Enfuvirtide (Fuzeon) Maraviroc (Selzentry)

74 Antiretroviral drugs 4. Integrase Inhibitor Raltegravir (Isentress)

75 Combination Formulations of Antiretroviral Drugs Combivir: Zidovudine + Lamivudine Epzicom: Zidovudine + Abacavir Trizivir: Zidovudine + Lamivudine +Abacavir Truvada: Tenofir +Emtricitabine Atripla: Tenofovir + Emtricitabine + Efavirenz

76 Principles of Therapy of HIV 1. Ongoing HIV replicatio leads to immne system damage and progression to AIDS. 2. Plasma HIV RNA levels indicate the magnitude of HIV replication and the rate of CD4+ T cell destruction. 3. Treatment decisions based upon plasma HIV RNA levels and CD4+ T cell counts. 4. Maximal suppression of viral replication is a goal of therapy. 5. The antiretroviral drugs used in combination regimens.

77 Influenza Acute respiratory illness Influenza viruses Fever, headache, myalgia, weakness Outbreaks: winter

79 Etiologic Agent Orhtomyxoviridae family Influenza A, B, and C viruses

80 Clinical manifestations Abrupt onset of systemic symptoms Cough, sore throat Fever C Physical findings minimal Uncomplicated influenza resolves 2-5 days

82 Complications Pneumonia: primary influenza pneumonia, secondary bacterial pneumonia, or both Exacerbation of COPD and asthma Rarely myositis

83 Laboratory Findings Virus may be detected: throat swabs, sputum Tissue culture for virus isolation

84 Treatment Bed rest,acetaminophen Antiviral therapy Amantadine Rimantadine Zanamivir Oseltamivir

86 Prophylaxis Inactivated and live attenuated vaccines 50-80% protection Inactivated vaccines safely administered to immuncompromised patients Before influenza outbreaks

Human Herpes Viruses (HHV) Mazin Barry, MD, FRCPC, FACP, DTM&H Assistant Professor and Consultant Infectious Diseases KSU

Human Herpes Viruses (HHV) Mazin Barry, MD, FRCPC, FACP, DTM&H Assistant Professor and Consultant Infectious Diseases KSU HERPES VIRUS INFECTIONS objectives: ØTo know the clinically important HHVs. ØTo